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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00947115




Registration number
NCT00947115
Ethics application status
Date submitted
16/07/2009
Date registered
27/07/2009
Date last updated
30/10/2020

Titles & IDs
Public title
Evaluation of Long-term Immunogenicity and Safety of a Human Papillomavirus (HPV) Vaccine in Healthy Female Subjects
Scientific title
Follow-up Study to Evaluate the Long-term Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV (580299) Vaccine in Healthy Female Subjects
Secondary ID [1] 0 0
2009-011357-41
Secondary ID [2] 0 0
112772
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Infections, Papillomavirus 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Blood sampling
Treatment: Surgery - Cervico-vaginal secretion (CVS) samples
Treatment: Drugs - CP-868,596
Treatment: Drugs - Docetaxel
Treatment: Drugs - CP-868,596
Treatment: Drugs - Docetaxel
Treatment: Drugs - CP-868,596
Treatment: Drugs - Docetaxel
Treatment: Drugs - CP-868,596
Treatment: Drugs - AG-013736
Treatment: Drugs - Docetaxel
Treatment: Drugs - GS-9411
Treatment: Drugs - Placebo
Treatment: Drugs - vemurafenib

Experimental: Cervarix 15-25 years group - Women, aged 15 to 25 at the time of primary vaccination, who were vaccinated with Cervarix intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule in the primary study HPV-014 (NCT00196937).

Experimental: Cervarix 26-45 years group - Women, aged 26 to 45 at the time of primary vaccination, who were vaccinated with Cervarix intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule in the primary study HPV-014 (NCT00196937).

Experimental: Cervarix 46-55 years group - Women, aged 46 to 55 at the time of primary vaccination, who were vaccinated with Cervarix intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule in the primary study HPV-014 (NCT00196937).

Experimental: Cohort 1 - 60 mg BID/ 75 mg/m2

Experimental: Cohort 2 - 100 mg BID/75 mg/m2

Experimental: Cohort 3 - 100 mg BID/100 mg/m2

Experimental: Cohort 4b - CP-868,596 + AG-013736 + TXT 75

Placebo comparator: 5 - Placebo


Treatment: Surgery: Blood sampling
Blood samples were collected at Years 5, 6, 7, 8, 9 and 10.

Treatment: Surgery: Cervico-vaginal secretion (CVS) samples
CVS samples were collected at Years 5, 6, 7, 8, 9 and 10 in subjects who volunteered for this procedure.

Treatment: Drugs: CP-868,596
Oral tablet 60 mg BID continuous

Treatment: Drugs: Docetaxel
Intravenous 75 mg/m2 every three weeks

Treatment: Drugs: CP-868,596
Oral tablet 100 mg BID continuous

Treatment: Drugs: Docetaxel
Intravenous 75 mg/m2 every three weeks

Treatment: Drugs: CP-868,596
Oral tablet 100 mg BID continuous

Treatment: Drugs: Docetaxel
Intravenous 100 mg/m2 every three weeks

Treatment: Drugs: CP-868,596
Oral tablet 60 mg BID continuous

Treatment: Drugs: AG-013736
Oral tablet 5 mg BID continuous

Treatment: Drugs: Docetaxel
Intravenous 75 mg/m2 every three weeks

Treatment: Drugs: GS-9411
Inhaled GS-9411 dissolved in sterile saline

Treatment: Drugs: Placebo
Inhaled placebo in sterile saline

Treatment: Drugs: vemurafenib
960 mg b.i.d. continuous oral dosing
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Anti-Human Papillomavirus (Anti-HPV)-16/18 Antibody Titers in Serum at Years 5, 6 and 7
Timepoint [1] 0 0
At Years 5, 6 and 7
Primary outcome [2] 0 0
Anti-HPV-16/18 Antibody Titers in Serum at Years 8, 9 and 10
Timepoint [2] 0 0
At Years 8, 9 and 10
Primary outcome [3] 0 0
Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies at Years 5, 6 and 7
Timepoint [3] 0 0
At Years 5, 6 and 7
Primary outcome [4] 0 0
Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies at Years 8, 9 and 10
Timepoint [4] 0 0
At Years 8, 9 and 10
Primary outcome [5] 0 0
First-cycle Dose Limiting Toxicities
Timepoint [5] 0 0
2.5 years
Primary outcome [6] 0 0
Safety and Tolerability of 4 escalating doses of GS-9411 in healthy male volunteers
Timepoint [6] 0 0
7 Days
Primary outcome [7] 0 0
Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [7] 0 0
From first treatment through September 27, 2010
Secondary outcome [1] 0 0
Anti-HPV-16/18 Secretion Antibody Titers in Cervico-vaginal Secretion (CVS) Samples at Years 5 and 6 in a Subset of Subjects
Timepoint [1] 0 0
At Year 5 and Year 6
Secondary outcome [2] 0 0
Anti-HPV-16/18 Secretion Antibody Titers in CVS Samples at Years 7, 8, 9 and 10 in a Subset of Subjects
Timepoint [2] 0 0
At Years 7, 8, 9 and 10
Secondary outcome [3] 0 0
Total Immunoglobulin G (IgG) Secretion Antibody Titers in CVS Samples at Years 5 and 6 in a Subset of Subjects
Timepoint [3] 0 0
At Year 5 and Year 6
Secondary outcome [4] 0 0
Total IgG Secretion Antibody Titers in CVS Samples at Years 7, 8, 9, and 10 in a Subset of Subjects
Timepoint [4] 0 0
At Years 7, 8, 9 and 10
Secondary outcome [5] 0 0
Total IgG Antibody Titers in Serum at Years 5, 6 and 7 Based on the ATP Cohort for Immunogenicity
Timepoint [5] 0 0
At Years 5, 6 and 7
Secondary outcome [6] 0 0
Total IgG Antibody Titers in Serum at Years 8, 9 and 10 Based on the ATP Cohort for Immunogenicity
Timepoint [6] 0 0
At Years 8, 9 and 10
Secondary outcome [7] 0 0
Total IgG Antibody Titers in Serum at Years 5, 6 and 7 Based on the TVC
Timepoint [7] 0 0
At Years 5, 6 and 7
Secondary outcome [8] 0 0
Total IgG Antibody Titers in Serum at Years 8, 9 and 10 Based on the TVC
Timepoint [8] 0 0
At Years 8, 9 and 10
Secondary outcome [9] 0 0
Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 4 in Primary Study HPV-014 (NCT00196937) to Year 5 in the Present Study
Timepoint [9] 0 0
From Year 4 in primary study HPV-014 (NCT00196937) up to Year 5 in present HPV-060 study
Secondary outcome [10] 0 0
Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 5 to Year 6
Timepoint [10] 0 0
From Year 5 up to Year 6
Secondary outcome [11] 0 0
Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 6 to Year 7
Timepoint [11] 0 0
From Year 6 up to Year 7
Secondary outcome [12] 0 0
Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 7 to Year 8
Timepoint [12] 0 0
From Year 7 up to Year 8
Secondary outcome [13] 0 0
Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 8 to Year 9
Timepoint [13] 0 0
From Year 8 up to Year 9
Secondary outcome [14] 0 0
Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 9 to Year 10
Timepoint [14] 0 0
From Year 9 up to Year 10
Secondary outcome [15] 0 0
Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 0 to Year 10
Timepoint [15] 0 0
From Year 0 up to Year 10
Secondary outcome [16] 0 0
Determine the safety and tolerability of the combination of daily CP-868,596 and docetaxel on an every 3-week schedule
Timepoint [16] 0 0
2.5 years
Secondary outcome [17] 0 0
Determine the safety and tolerability of the combination of daily CP-868,596 plus daily AG-013736 plus docetaxel on an every 3-week schedule
Timepoint [17] 0 0
2.5 years
Secondary outcome [18] 0 0
To evaluate the pharmacokinetics (PK) of CP-868,596 and docetaxel when given in combination
Timepoint [18] 0 0
2.5 years
Secondary outcome [19] 0 0
To evaluate the pharmacokinetics (PK) of CP-868,596, AG-013736 and docetaxel when given in combination
Timepoint [19] 0 0
2.5 years
Secondary outcome [20] 0 0
Conduct biomarker investigations on plasma/serum samples to explore critical events in pharmacodynamic response to CP-868,596 (eg, VEGF, phospho-SHP, etc.)
Timepoint [20] 0 0
2.5 years
Secondary outcome [21] 0 0
To explore the relationship between polymorphisms in genes involved in the metabolism and transport of CP-868,596 and pharmacokinetic/pharmacodynamic parameters
Timepoint [21] 0 0
2.5 years
Secondary outcome [22] 0 0
To explore the effects of CP-868,596 on tumor blood flow and permeability via DCE-MRI
Timepoint [22] 0 0
2.5 years
Secondary outcome [23] 0 0
To assess any preliminary clinical evidence of anti-tumor activity using RECIST
Timepoint [23] 0 0
2.5 years
Secondary outcome [24] 0 0
Decrease in mean Fasting Plasma Glucose (FPG)
Timepoint [24] 0 0
At week 24
Secondary outcome [25] 0 0
Mean change in body weight
Timepoint [25] 0 0
At week 24
Secondary outcome [26] 0 0
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [26] 0 0
From first treatment through September 27, 2010
Secondary outcome [27] 0 0
Duration of Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [27] 0 0
From first treatment through September 27, 2010
Secondary outcome [28] 0 0
Time to Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [28] 0 0
From first treatment through September 27, 2010
Secondary outcome [29] 0 0
Progression Free Survival (PFS) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Timepoint [29] 0 0
From first treatment through September 27, 2010
Secondary outcome [30] 0 0
Overall Survival
Timepoint [30] 0 0
From first treatment through September 27, 2010
Secondary outcome [31] 0 0
Improvement in Physical Symptoms (Improvement in Physician's Assessment of Global Performance Status and Oxygen Saturation Requirements, and Decrease in Total Dose and Frequency of Narcotic Pain Analgesics) During Treatment in Comparison to Baseline
Timepoint [31] 0 0
From first treatment through September 27, 2010
Secondary outcome [32] 0 0
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 of Cycle 1
Timepoint [32] 0 0
Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
Secondary outcome [33] 0 0
Vemurafenib Plasma Level Area Under the Curve From 0 to 8 Hours (AUC0-8h) on Day 15 of Cycle 1
Timepoint [33] 0 0
Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
Secondary outcome [34] 0 0
Vemurafenib Plasma Levels at Various Treatment Cycles
Timepoint [34] 0 0
Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
Secondary outcome [35] 0 0
Time-matched Change From Baseline in the Study Specific Corrected QT Interval (QTcP)
Timepoint [35] 0 0
Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
Secondary outcome [36] 0 0
Percentage of Patients With Adverse Event
Timepoint [36] 0 0
From first treatment through September 27, 2010

Eligibility
Key inclusion criteria
* Subjects who the investigator believed that they could and would comply with the requirements of the protocol.
* A female who had been enrolled in NCT00196937 study and received three doses of HPV-16/18 vaccine.
* Written informed consent obtained from the subject.
Minimum age
20 Years
Maximum age
60 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
* Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs occurring less than three months prior to blood sampling.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.
* Administration or planned administration of any HPV vaccine, other than the three doses of HPV-16/18 vaccine administered in NCT00196937 study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/02/2015
Sample size
Target
Accrual to date
Final
525
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - East Melbourne
Recruitment hospital [2] 0 0
Nucleus Network, Ltd. - Melbourne
Recruitment hospital [3] 0 0
Sanofi-Aventis Administrative Office - Macquarie Park
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Bayern
Country [2] 0 0
Germany
State/province [2] 0 0
Berlin
Country [3] 0 0
Poland
State/province [3] 0 0
Bydgoszcz
Country [4] 0 0
Poland
State/province [4] 0 0
Poznan
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
California
Country [7] 0 0
United States of America
State/province [7] 0 0
Colorado

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Infection with human papillomavirus (HPV) has been clearly established as the necessary cause of cervical cancer. This study is designed to evaluate the long-term immunogenicity and safety of the GSK Biologicals' 580299 HPV vaccine up to 10 years after administration of the first dose of HPV vaccine (Month 0) in primary study NCT00196937. This protocol posting deals with objectives \& outcome measures of the extension phase from Year 5 to Year 10. The objectives \& outcome measures of the primary phase and extension phase up to year 4 are presented in a separate protocol posting (NCT00196937).
Trial website
https://clinicaltrials.gov/study/NCT00947115
Trial related presentations / publications
Schwarz T, Spaczynski M, Kaufmann A, Wysocki J, Galaj A, Schulze K, Suryakiran P, Thomas F, Descamps D. Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15-55 years and first-time modelling of antibody responses in mature women: results from an open-label 6-year follow-up study. BJOG. 2015 Jan;122(1):107-18. doi: 10.1111/1471-0528.13070. Epub 2014 Sep 11.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00947115